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A modified technique for purely laparoscopic liver transplantation in a porcine model

Year: 2025

Type: article

Abstract: To the Editor: Laparoscopic hepatectomy techniques have been applied in living-donor hepatectomy, primarily due to their minimally invasive nature.[1] However, whether laparoscopic techniques can be used effectively for the procedure of liver transplant recipient remains to be explored. In July 2021, Suh et al[2] reported the first case of a purely laparoscopic procedure for liver transplant recipients, with an operative time of 960 min. In April 2022, they reported an improved case of laparoscopic explant hepatectomy followed by robot-assisted graft implantation, with a decreased operative time of 740 min. Both recipients were discharged with no major complications.[3] These reports have attracted widespread attention; however, the excessively long operative durations have raised concerns. Nevertheless, they represent pioneering steps toward purely laparoscopic liver transplantation (PLLT). However, the long operative times reported in clinical cases suggest that PLLT is not yet applicable clinically. Presently, there are considerable challenges in performing PLLT, including a lack of adequate operative field exposure, vessel and bile duct anastomoses, acceptable operative duration, streamlined surgical procedures, and the availability of appropriate instruments. Addressing these challenges requires further experimental studies in animal models, particularly pigs, whose visceral anatomy, size, and abdominal cavity closely resemble those of humans. Therefore, this study aimed to establish a porcine model of PLLT to explore suitable procedures, train liver transplant surgeons, facilitate the development of specialized surgical instruments, and pave the way for clinical PLLT. Twenty-seven pairs of Bama miniature pigs were used as liver donors and recipients. The animals were categorized into two groups: A classic group (the first 11 pairs) and a modified group (the subsequent 16 pairs). Pigs in the classic group underwent procedures simulating human classic orthotopic liver transplantation (LT) under endoscopy, while those in the modified group underwent endoscopic procedures in which the reconstructions of the suprahepatic inferior vena cava (IVC) and portal vein were prioritized, followed by prompt liver graft revascularization. A 3D-printed specially designed liver transfer device (3D-PSDLTD) was employed to facilitate liver graft import. The pigs were provided by the Experimental Animal Center of Jiangsu Langyue Biotechnology Co., Ltd. (Taixing, Jiangsu, China). This study was conducted in accordance with the national and international guidelines, including the “Guide for the Care and Use of Laboratory Animals” published by the National Institutes of Health, and adhered to the Animal Research: Reporting of in vivo Experiments guidelines. The pigs were not fed for 48 h preoperatively but had unrestricted access to water. Recipient pigs had arterial and venous lines placed under ultrasound guidance. They were euthanized after anesthesia with pentobarbital sodium at the end of the experiment. Anesthesia was induced with propofol (1 mg/kg) and maintained with inhaled isoflurane administered via tracheal intubation. The tidal volume was set at 10 mL/kg body weight. The donor livers were procured and prepared on a back table using the previously described methods,[4] and were preserved in ice water at 0–4 °C. The recipient’s liver was removed using the following procedures. Three 12 mm trocars and two 5 mm trocars were inserted [Supplementary Figure 1A, https://links.lww.com/CM9/C665], and pneumoperitoneum was maintained at 12 mmHg. The bile duct was isolated and transected at its distal end [Supplementary Figure 2A, https://links.lww.com/CM9/C665]. The left and right branches of the hepatic artery and portal vein were isolated and encircled with vessel loops, and the right and left liver lobes were mobilized. Both the suprahepatic and infrahepatic IVCs were isolated and encircled using vessel loops. An 11 cm suprapubic transverse incision was made in advance and covered with an incision cover (PQA60/70-60/150; Weizhi Suzhou Medical Technology Co., Ltd.) to facilitate liver removal and graft import [Supplementary Figure 1B, https://links.lww.com/CM9/C665]. The pneumoperitoneum was established immediately after closing the incision cover [Supplementary Figure 1C, https://links.lww.com/CM9/C665]. Two incisions were made inferior to the right and left costal arches for the subsequent clamping of the suprahepatic and infrahepatic IVCs [Supplementary Figure 1D, https://links.lww.com/CM9/C665]. The branches of the hepatic artery were clipped distal to the bifurcation and transected [Supplementary Figure 2B, https://links.lww.com/CM9/C665]. The portal vein was clamped with a medium-sized bulldog clamp [Supplementary Figure 2C, https://links.lww.com/CM9/C665] and transected close to its bifurcation after clamping with two biological clips [Supplementary Figure 2D, https://links.lww.com/CM9/C665]. The infrahepatic IVC was clamped near the renal vein using an atraumatic vascular clamp [Supplementary Figure 2E, https://links.lww.com/CM9/C665] and transected with an endovascular stapler distal to the clamp [Supplementary Figure 2F, https://links.lww.com/CM9/C665]. The suprahepatic IVC was clamped close to the diaphragm using an aortic clamp [Supplementary Figure 2G, https://links.lww.com/CM9/C665]. The retrohepatic IVC was isolated and transected distal to the aortic clamp after the right, middle, and left hepatic veins were isolated and transected [Supplementary Figure 2H, https://links.lww.com/CM9/C665]. The native liver was then moved to the pelvic cavity. The operative field was stanched thoroughly. Liver grafts were implanted according to the following procedures. The incision cover was opened, the native liver was removed, and the liver graft was promptly introduced to the right inferior diaphragm, and pneumoperitoneum was restored immediately after closing the incision cover [Supplementary Video]. The liver graft was adjusted to the appropriate position for suprahepatic IVC reconstruction. The portal vein flush catheter was withdrawn from the incised portion of the left abdominal wall and connected to cold Ringer’s solution to flush the liver graft. In the classic group, the liver grafts were implanted using the previously described methods [Figure 1A–E].[4] The liver graft flush was discontinued before anastomosis of the intrahepatic IVC was completed. In the modified group, 3D-PSDLTD was used to import the liver grafts [Figure 1F and G, Supplementary Video]. Reconstruction of the suprahepatic IVC and portal vein was prioritized, followed by prompt liver graft revascularization [Figure 1H]. The common bile ducts in both groups were anastomosed to the recipient’s duodenum over a stent using intermittent sutures(with 5-0 Polydioxanone Suture) [Figure 1E].Figure 1: Liver graft implantation process. (A) Suprahepatic IVC anastomosi (yellow arrow). (B) Infrahepatic IVC anastomosis (yellow arrow). (C) Portal vein anastomosis (yellow arrow). (D) Hepatic artery anastomosis (yellow arrow). (E) Choledochoduodenostomy (yellow arrow). (F) 3D printed specially designed liver graft transfer device (yellow arrow). (G) Transferring the liver graft into the right inferior diaphragm (yellow arrow). (H) Revascularizing the liver graft. IVC: Inferior vena cava. {"href":"Single Video Player","role":"media-player-id","content-type":"play-in-place","position":"float","orientation":"portrait","label":"Supplementary Video","caption":"Purely Laparoscopic Liver Transplantation in a Porcine Model","object-id":[{"pub-id-type":"doi","id":""},{"pub-id-type":"other","content-type":"media-stream-id","id":"1_uwdvcwff"},{"pub-id-type":"other","content-type":"media-source","id":"Kaltura"}]} General characteristics, completion rates and procedure duration, vessel and bile duct anastomoses, rate of liver graft revascularization, and anhepatic and warm ischemic times were compared between the two groups. Quantitative data are presented as mean ± standard deviation. Statistical differences between the two groups were determined using a two-tailed unpaired Student’s t-test. A P-value <0.05 was considered statistically significant. All analyses were performed using SPSS software (version 25.0; SPSS, Chicago, IL, USA). The general characteristics of the recipients and donors are presented in Supplementary Table 1, https://links.lww.com/CM9/C665. No significant differences were observed between the classic and modified groups (all P >0.05). The procedure was successfully completed in 1 of the 11 recipient pigs in the classic group and in 5 of the 16 pigs in the modified group. The procedure completion rates in the two groups (9% vs. 31%) were not significantly different (P >0.05). The total procedure completion rate in both groups was 22.2% (6/27). The anastomosis completion rates of the suprahepatic IVC, infrahepatic IVC, portal vein, hepatic artery, and bile duct were 64% (7/11), 64% (7/11), 55% (6/11), 9% (1/11), and 9% (1/11), respectively, in the classic group, and 88% (14/16), 81% (13/16), 88% (14/16), 56% (9/16), and 31% (5/16), respectively, in the modified group. No significant differences were observed between the two groups (all P >0.05), except for the hepatic arteries (P <0.05). The time required for reconstruction of the suprahepatic IVC, infrahepatic IVC, portal vein, hepatic artery, and bile duct were 35.4 ± 22.4, 35.4 ± 15.6, 34.3 ± 11.3, 32, and 15 min, respectively, in the classic group; and 25.8 ± 9.1, 30.8 ± 13.6, 30.2 ± 8.4, 43 ± 15.5, and 21.4 ± 2.2 min, respectively, in the modified group. No significant differences were observed between the two groups (all P >0.05). The liver graft revascularization rates were 55% (6/11) in the classic group and 88% (14/16) in the modified group. No significant differences were observed between the two groups (P >0.05). The anhepatic time was shorter in the modified group (107.4 ± 29.5 min) than in the classical group (153.9 ± 26.7 min, P <0.01). The warm ischemic time was shorter in the modified group (90.3 ± 3.9 min, N = 11) than in the classic group (134.0 ± 5.3 min, N = 7, P <0.01). The operative time was 450 min in the classic group and 457 ± 90.8 min in the modified group. Reported complications included one case of bleeding from the infrahepatic IVC anastomosis in the classic group, one case of simultaneous stenosis and thrombus in the portal vein anastomosis, and one case of stenosis in the suprahepatic IVC anastomosis in the modified group. Twenty recipient pigs (six in the classic group and 14 in the modified group) had non-anastomotic bleeding in the operative field after their liver grafts were revascularized [Supplementary Table 1, https://links.lww.com/CM9/C665]. In this study, we successfully established a porcine model for PLLT. We developed a feasible surgical procedure for PLLT and further improved it by procedure improvement and 3D-PSDLTD application. The procedure improvement, along with the 3D-PSDLTD application, resulted in shorter anhepatic time and warm ischemic time in the modified group. Despite these advancements, the overall liver graft revascularization rate in the two groups (74%, 20/27) was relatively low, and the anhepatic phase time was significantly longer (153.9 min) in the classic group than in the modified group (107.4 min). Only 22.2% (6/27) of the recipient pigs completed the transplantation procedure, and the operative time for the pigs that completed the procedure exceeded 450 min. Non-anastomotic bleeding was observed in the operative field of 20 recipient pigs after the liver grafts were revascularized. These results indicate that establishing a porcine PLLT model is challenging. The low procedural success rate and prolonged operative time in this porcine model, along with the extended anhepatic phases and operative times reported in clinical cases,[2,3] suggest that PLLT is not yet clinically viable. The classic group reported difficulties in graft transfer, limited operative field exposure, complexity in vessel and bile duct anastomoses, and the need for finer vascular forceps, scissors, clamps, and needle holders with narrow tips. In the classic group, we found that flatulence became severe after suprahepatic IVC reconstruction, and operative field exposure became very difficult. We addressed these limitations in the modified group by prioritizing the reconstruction of the suprahepatic IVC and portal vein, followed by prompt liver graft revascularization. This approach quickly reduced flatulence and improved operative field exposure. The liver grafts were contained in the 3D-PSDLTD along with crushed ice. This facilitated the liver graft transport and ensured continuous hypothermic preservation, improved operative field exposure, and facilitated the vessel and bile duct anastomoses. Skillful surgical techniques, such as laparoscopic suturing and knot tying remain essential for successful PLLT. Inexperienced surgeons can be trained using this porcine model. Less proficient laparoscopic techniques, incomplete perioperative management, lack of suitable instruments, non-veno-venous bypass approaches, and a limited number of cases have resulted in a low success rate and poor survival of recipient pigs. Nevertheless, the porcine model of PLLT remains ideal for exploring applicable surgical procedures, training surgical techniques, and developing suitable instruments tailored for PLLT. Conflicts of interest None.

Source: Chinese Medical Journal

DOI: 10.1097/cm9.0000000000003873